A speech fluency brain network derived from gliomas.

The brain network of speech fluency has not yet been investigated via a study with a large and homogenous sample. This study analysed multimodal imaging data from 115 patients with low-grade glioma to explore the brain network of speech fluency. We applied voxel-based lesion-symptom mapping to identify domain-specific regions and white matter pathways associated with speech fluency. Direct cortical stimulation validated the domain-specific regions intra-operatively. We then performed connectivity-behaviour analysis with the aim of identifying connections that significantly correlated with speech fluency. Voxel-based lesion-symptom mapping analysis showed that damage to domain-specific regions (the middle frontal gyrus, the precentral gyrus, the orbital part of inferior frontal gyrus and the insula) and white matter pathways (corticospinal fasciculus, internal capsule, arcuate fasciculus, uncinate fasciculus, frontal aslant tract) are associated with reduced speech fluency. Furthermore, we identified connections emanating from these domain-specific regions that exhibited significant correlations with speech fluency. These findings illuminate the interaction between domain-specific regions and 17 domain-general regions-encompassing the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and rolandic operculum, superior temporal gyrus, temporal pole, inferior temporal pole, middle cingulate gyrus, supramarginal gyrus, fusiform gyrus, inferior parietal lobe, as well as subcortical structures such as thalamus-implicating their collective role in supporting fluent speech. Our detailed mapping of the speech fluency network offers a strategic foundation for clinicians to safeguard language function during the surgical intervention for brain tumours.

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM. PATIENTS AND METHODS: Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150-200 mg/m2, orally, every day (QD) d1-5/4 wk) and anlotinib (10 mg, orally, QD, d1-14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27-68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6-99.3]. The disease control rate was 95.2% (95% CI, 76.2-99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9-9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3-84.6). The median overall survival was 16.9 months (95% CI, 7.8-26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study. CONCLUSIONS: Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.

Decoding and synthesizing tonal language speech from brain activity.

Recent studies have shown that the feasibility of speech brain-computer interfaces (BCIs) as a clinically valid treatment in helping nontonal language patients with communication disorders restore their speech ability. However, tonal language speech BCI is challenging because additional precise control of laryngeal movements to produce lexical tones is required. Thus, the model should emphasize the features from the tonal-related cortex. Here, we designed a modularized multistream neural network that directly synthesizes tonal language speech from intracranial recordings. The network decoded lexical tones and base syllables independently via parallel streams of neural network modules inspired by neuroscience findings. The speech was synthesized by combining tonal syllable labels with nondiscriminant speech neural activity. Compared to commonly used baseline models, our proposed models achieved higher performance with modest training data and computational costs. These findings raise a potential strategy for approaching tonal language speech restoration.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

Clinical applications of neurolinguistics in neurosurgery.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.

Intraoperative Cognitive Mapping Tasks for Direct Electrical Stimulation in Clinical and Neuroscientific Contexts.

Direct electrical stimulation (DES) has been widely applied in both guidance of lesion resection and scientific research; however, the design and selection of intraoperative cognitive mapping tasks have not been updated in a very long time. We introduce updated mapping tasks for language and non-language functions and provide recommendations for optimal design and selection of intraoperative mapping tasks. In addition, with DES becoming more critical in current neuroscientific research, a task design that has not been widely used in DES yet (subtraction and conjunction paradigms) was introduced for more delicate mapping of brain functions especially for research purposes. We also illustrate the importance of designing a common task series for DES and other non-invasive mapping techniques. This review gives practical updated guidelines for advanced application of DES in clinical and neuroscientific research.

A Novel Intraoperative Brain Mapping Integrated Task-Presentation Platform.

BACKGROUND: To be efficient, intraoperative task-presentation systems must accurately present various language and cognitive tasks to patients undergoing awake surgery, and record behavioral data without compromising convenience of surgery. OBJECTIVE: To present an integrated brain mapping task-presentation system we developed and evaluate its effectiveness in intraoperative task presentation. METHODS: The Brain Mapping Interactive Stimulation System (Brain MISS) is a flexible task presentation system that adjusts for patient comfort, needs of the surgeon, and operating team, with multivideo recording for patients' behavior. A total of 48 patients from 3 centers underwent intraoperative language task test during awake brain surgery with the Brain MISS. Each patient was assigned 5 questions each on picture naming, reading, and listening comprehension before and during awake surgeries. The accuracy of intraoperative stimulus-response (without electrical stimulation) was recorded. The Brain MISS was to be considered effective, if the lower limit of 95% CI of patients' intraoperative response was ≥80% and also if the accuracy of intraoperative response of all patients was statistically higher than 80%. RESULTS: All patients successfully underwent intraoperative assessment with the Brain MISS. The overall accuracy of stimulus response was 95.8% (95% CI 90.18%-100.00%), with the lower limit being higher than 80% and the response accuracy also significantly being higher than 80% in all patients (P = .006). CONCLUSION: The Brain MISS is a portable and effective system for presenting and streamlining complicated language and cognitive tasks during awake surgery. It can also record standardized patient response data for neuroscientific research.

Germline ALK variations are associated with a poor prognosis in glioma and IDH-wildtype glioblastoma.

BACKGROUND: Glioma is the most common primary brain tumor. Clear classification is crucial for accurate diagnosis and individualized treatment. Histopathological characteristics and genetic alterations have shown to be related to prognosis and treatment response. Germline variants are important components of genetic alterations. However, the distribution of germline variations in glioma patients and their association with survival remain unknown. METHODS: We carried out whole-exome sequencing on 99 cases to explore germline variants in glioma. We also analyzed the association of germline variants with clinicopathological features and other prognostic indicators. RESULTS: All the glioma cases harbored rare germline variants. Germline ALK variants (gALK-Mut) were identified in 12/99 (12.12%) patients. The gALK-Mut patients had significantly shorter overall survival than germline ALK wildtype (gALK-WT) patients in the all glioma group (99 cases) and the subset of patients with IDH-wildtype glioblastoma (IDH-WT-GBM, 39 cases) (P = 0.013 and 0.027, respectively). The gALK-Mut patients also had higher frequency of BIRC5, PIK3CA and RPN1 somatic mutations than the gALK-WT patients in IDH-WT-GBM. Other confounding factors appeared to contribute to patient survival. The subgroup of patients in IDH-WT-GBM with gALK-Mut/TP53-Mut had worse prognosis than the gALK-WT/TP53-Mut subgroup (P = 0.031); The gALK-Mut/TERT-WT and gALK-Mut/TERT-Mut subgroups both had a worse prognosis than the gALK-WT/TERT-Mut subgroup (P = 0.031 and 0.018, respectively). CONCLUSIONS: Our study revealed ALK variation was an independent indicator of poor prognosis in glioma and IDH-WT-GBM. It could be a promising biomarker and tractable therapeutic target for this deadly disease.

Glioma surgery with awake language mapping versus generalized anesthesia: a systematic review.

Awake craniotomy with language mapping is being increasingly applied to avoid postoperative language dysfunctions worldwide. However, the effectiveness and reliability of this technique remain unclear due to the paucity of studies comparing the awake craniotomy with general anesthesia. To determine the benefit of awake craniotomy for language, motor, and neurological functions, as well as other clinical outcomes, we searched Medline, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database up to December 2019. Gray literatures were also searched. We included randomized and non-randomized controlled studies comparing awake craniotomy versus general anesthetic resection and reporting the language and neurological outcomes. Ten studies with 833 patients were included in the meta-analysis. The pooled risk ratio (RR) suggested no significant differences in language and neurological outcomes between general anesthesia group and awake craniotomy group without electrical stimulation. Awake craniotomy with electrical stimulation, however, was associated with improved late language and neurological outcomes (≥ 3 months) versus general anesthesia with pooled RR of 0.44 (95% CI = 0.20-0.96) and 0.49 (95% CI = 0.30-0.79), respectively. Awake craniotomy with electrical stimulation was also associated with better extent of resection with the pooled RR of 0.81 (95%CI = 0.71-0.92) and shorter hospital stay duration with the pooled weighted mean difference (WMD) of - 1.14 (95%CI = - 1.80 to - 0.48). This meta-analysis suggested that the application of awake craniotomy with electrical stimulation during glioma resection is associated with lower risks of long-term neurological and language deficits and higher extent of tumor resection, as well as shorter hospital stay duration.